Hallmarks of asthma include reversible airway obstruction, and non-specific airway hyperresponsiveness. Hyperresponsiveness not only determines the ease with which obstruction will occur, but also closely relates clinically with symptomatology. While the cause of asthma is still unknown, several classes of anti-asthma medications are currently available. Most treat bronchoconstriction, but do not reverse the accompanying hyperresponsiveness. Inhaled steroids can reverse hyperresponsiveness, but this effect can have a slow onset and generally requires at least daily administration of medication.
Evidence indicates that platelets in the peripheral blood are activated in-vivo during allergen induced attacks of asthma, and further indicates that platelets release a substance(s) which enhances basophil response to IgE dependent activation, Knauer et al., N Engl J Med 306: 1407 (1981), Knauer et al., Int Arch Allergy Appl Immunol 74:29 (1984). Further data suggest that a substance released by platelets could also directly cause basophil degranulation, potentially by an IgE dependent mechanism, Orchard et al., Thromb Haemostas 54:232 (1986); Orchard et al., J Immunol 136:22 (1986). Additional research has indicated that platelets are activated during exercise induced asthma, and that platelet activation is prevented by premedication with inhaled cromolyn, Johnson et al., Thorax 41: 290 (1986). A role for platelets with regard to allergic inflammation was further suggested by the finding that they can bind IgE via a low affinity receptor, thereby permitting direct activation by exposure to allergen, Cines et al., J Immunol 136: 3433-3440 (1986), and also that platelet depletion in rabbits reduces late phase asthmatic response, including hyperresponsiveness and eosinophilic inflammation. Coyle et al., Am Rev Respir Dis, 142:507-593 (1990).
It was recently shown that a protein produced by platelets, termed Platelet-Derived Histamine Releasing Factor (PD-HRF), causes basophil degranulation only in allergic subjects. See Fisher et al., J Allergy Clin Inmmunol 79:196 (1987). In-vivo skin testing in humans with PD-HRF obtained from platelet supernatant demonstrated that allergic asthmatics developed reactions, but normal subjects or subjects with allergic rhinitis without asthma did not. Weiss et al. J Allergy Clin. Immunol 81: 224 (1988). In a study designed to further define the role of PD-HRF in asthma, in-vivo bronchial challenges of allergic asthmatic rabbits using PD-HRF-containing supernatants caused early and late airway obstruction and increased hyperresponsiveness in the subjects. Fisher et al., Aspen Allergy Conference (1990); Metzger et al., J. Allergy Clin Immunol 85(1) (1990).